발기부전환자에서심혈관계위험인자와음경혈역동학적지표와의연관성 The Correlation between Cardiovascular Risk Factors and Penile Hemodynamic Parameters in Men with Erectile Dysfunction Woong Jin Bae, Dong Wan Sohn, Sung Dae Kim 1, Su Jin Kim, Sung-Hoo Hong, Ji Youl Lee, Yong-Hyun Cho, Sae Woong Kim From the Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, 1 School of Medicine, Cheju National University, Jeju, Korea Purpose: The cause of erectile dysfunction (ED) is mostly organic in nature and is associated with cardiovascular disease. Therefore, the presence of ED has been shown to be related to cardiovascular risk factors such as coronary artery disease, hypertension, diabetes mellitus (DM), and hyperlipidemia. This study evaluated the correlation between cardiovascular risk factors and penile hemodynamic parameters in men with ED. Materials and Methods: The relationship between vascular risk factors and penile hemodynamic parameters were evaluated in a total of 149 men with ED. The patients were stratified according to the type and number of risk factors present. Each patient underwent a penile duplex Doppler ultrasound study after injections of intracavernous prostaglandin E1 to evaluate penile blood flow parameters. The rates of arterial insufficiency, venoocclusive dysfunction, and nonvascular etiologies were also evaluated. These results were statistically compared with those from patients with ED without vascular risk factors. Results: The poorest blood flow was found in patients with ED with DM. Arterial insufficiency was most prevalent in patients with coronary artery disease and DM (p<0.05). Venoocclusive dysfunction was observed most often in hypertensive patients with ED. Abnormal penile blood flow parameters correlated with the number of vascular risk factors present. Conclusions: This study shows that cardiovascular risk factors are associated with abnormal penile blood flow. In addition, the number of risk factors is correlated with an increased probability of having abnormal blood flow parameters. (Korean J Urol 2009;50:689-693) Key Words: Erectile dysfunction, Cardiovascular diseases, Risk factor, Color doppler ultrasonography Korean Journal of Urology Vol. 50 No. 7: 689-693, July 2009 DOI: 10.4111/kju.2009.50.7.689 가톨릭대학교, 1 제주대학교의과대학비뇨기과학교실 배웅진ㆍ손동완ㆍ김성대 1 김수진ㆍ홍성후ㆍ이지열조용현ㆍ김세웅 Received:February 11, 2009 Accepted:July 2, 2009 Correspondence to: Sae Woong Kim Department of Urology, Seoul St. Mary s Hospital, 505, Banpodong, Seocho-gu, Seoul 137-701, Korea TEL: 02-2258-1071 FAX: 02-2258-1080 E-mail: ksw1227@catholic.ac.kr C The Korean Urological Association, 2009 서론발기부전은 만족스런성생활을누리는데필요한발기를얻지못하거나유지할수없는상태 ' 를의미하며이로인한삶의질저하와스트레스로많은남성들이불편을호소하고있다. 1 Feldman 등 2 은메사추세츠남성노화연구에서, 일 반대중을대상으로성기능에대한역학조사를시행하였으며, 이를통해발기부전에대한유병률과생리적, 정신적연관관계를규명하였고발기부전에대한표준자료를제시하였다. 이에따르면 40-70세의남자중발기부전유병률은 52% 라하였으며, 중등도이상의발기부전이 35% 라고하였다. 국내의경우 40-79세사이의 1,570명을대상으로한역학조사에서 13.4% 의환자가발기부전을호소했으며, 32.4% 689
690 Korean Journal of Urology vol. 50, 689-693, July 2009 에서설문조사를통해발기부전이진단되었다. 3 이러한발기부전의원인중 80% 이상은기질적원인이며, 이중많은부분을혈관성발기부전이차지하고있는데, 4 이는해면체로유입되는동맥의혈류가감소하거나정맥폐쇄기능의장애로인해해면체내에혈액이충만하지못함으로발생하게된다. 5 또한이들의대다수가고혈압, 당뇨병, 고지혈증, 흡연, 비만등심혈관계질환의위험인자들을적어도한가지이상가지고있고, 2,6-8 심혈관계질환을가진환자들에서발기부전의유병률이일반인구에비하여높다는사실이보고되면서심혈관계질환과혈관성발기부전의연관성에대한관심이높아지고있다. 9,10 국내에서도 2,519명의인구를기준으로한코호트연구에서음주, 운동습관, 금연등의생활습관은발기부전의위험도와의연관성이확실치않았으나, 고혈압, 240 mg/dl 이상의고콜레스테롤혈증, 흡연등심혈관질환의위험인자들이발기부전과관련이있었다. 11 음경의혈류역동학과발기의기전에대한이해가높아지면서, 다양한진단방법중음경도플러초음파가혈관성발기부전을비교적정확하게평가할수있는검사방법으로인정받고있는데, 12,13 Kendirci 등 14 은심혈관계위험인자와비정상음경혈류지표간의상관관계에대해보고하였으며위험인자의수와비정상혈류지표의정도간에도양의상관관계가있다고하였다. 발기부전진단시음경도플러초음파검사를시행한환자에서, 혈역동학적지표와심혈관계위험인자사이의연관관계에대해알아본연구가국내의경우는시행된바가없어이를조사해보았다. 대상및방법 2000년 1월부터 2007년 12월까지발기부전을주소로내원하여음경도플러초음파검사를시행한환자를대상으로음경의혈역동학적지표와심혈관계위험인자사이의연관성에대해후향적으로조사하였다. 골반, 음경, 요도및전립선에수술또는손상의과거력이있거나, 정상적인성행위가불가능한환자를제외한 149명의환자를대상으로하였다. 모든대상자는고혈압, 당뇨병등을포함한병력에대한문진을실시하였고혈압과키, 몸무게를측정하였으며공복혈당, 전콜레스테롤치등의혈액검사를실시하였다. 고혈압은 Joint National Committee 보고서를기준으로하여수축기혈압 120 mmhg 미만, 이완기혈압 80 mmhg 미만을정상으로하였으며공복시혈당치는미국당뇨학회의기준치로하였고, 고지혈증의정의는미국 National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III를 참고하였다. 15,16 환자의체중 (kg) 을키 (meter) 의제곱으로나누어환자의체질량지수 (body mass index; BMI) 를구하였으며 World Health Organization (WHO) 의기준에근거하여 25 kg/m 2 이상을비만으로정의하였다. 17 음경도플러초음파는 prostaglandin E1 10-20μg 을음경해면체에주사한후자기자극 (self stimulation) 을시행하면서최고수축기혈류속도와이완기말혈류속도, 저항계수를측정하였으며결과에따라최고수축기혈류속도 25 cm/s 미만인동맥성발기부전, 이완기말혈류속도 5 cm/s 이상인정맥폐쇄성발기부전, 두소견이동시에관찰되는복합성발기부전과정상범위의혈역동학적지표소견을보이는비혈관성발기부전으로나누었다. 18 심혈관질환과관련된대표적질환인고혈압, 당뇨병, 고지혈증, 관상동맥질환등의과거력이있는환자를대상으로각한가지위험인자군에서혈역동학적지표의특성에대해알아보았고, 심혈관질환과관련된생활습관중흡연과비만여부를위험인자에추가하여위험인자수가음경혈류에미치는영향을조사하였다. 통계분석은 SPSS version 12.0 (SPSS Inc, Cambridge, USA) 을이용하였으며, chi-square test와분산분석 (one-way ANOVA) 을이용하여단일위험인자간발기부전의특성과위험인자수에따른혈역동학적지표의특성을분석하였고 p값이 0.05 미만인경우에유의한차이가있다고평가하였다. 결과환자군의평균나이는 50.65세 (20-72) 였으며비혈관성발기부전은 52명 (35%) 이었고혈관성발기부전으로진단된경우가 97명 (65%) 이었다. 이들중동맥성 54명, 정맥폐쇄성은 37명이었는데그중 11명의환자는심혈관과관련된질환이없었으며, 67명이단일위험인자를가지고있었고, 71명이 2개이상의심혈관계위험인자가있었다. 단일위험인자간의비교에서관련질환의빈도는고혈압이가장많았고, 고지혈증이다음을차지했는데그중최고수축기혈류속도는당뇨병환자에서 24.7±6.7 cm/s로가장불량하였고, 이완기말혈류속도는고혈압환자에서 4.9±2.6 cm/s로가장높았다 (Table 1). 비혈관성발기부전은심혈관인자가없었던환자군에서유병률이높아유의한차이를보였으며 (p<0.05), 동맥성발기부전은관상동맥질환 (66.7%) 과당뇨병 (66.7%) 에서유의하게높았다 (p<0.05). 그러나정맥폐쇄성발기부전의경우고지혈증 (44.4%) 에서고혈압 (22.6%), 관상동맥질환 (22.2%) 과당뇨병 (11.1%) 에비해유병률이높았으나통계적으로유의하지는않았다 (p=0.180). 심혈관질환과관련된생활습관중흡연과비만여부를
Woong Jin Bae, et al:correlation between Cardiovascular Risk Factor and ED 691 Table 1. Characteristics of men with ED with a single vascular risk factor No VRFs Hypertension CAD DM Dyslipidemia p-value No./total No. of patients (%) Age PSV EDV AI (%) a VOD (%) Nonvascular state (%) a 11/149 (7.4) 48.5±6.7 40.6±12.0 3.3±2.9 18.2 9.1 72.7 31/67 (46.3) 51.0±6.9 36.7±15.1 4.9±2.6 22.6 22.6 31 9/67 (13.4) 51.0±10.9 30.0±13.5 4.7±0.6 66.7 22.2 9 9/67 (13.4) 53.3±6.9 24.7±6.7 4.1±0.9 66.7 11.1 9 18/67 (26.9) 53.1±8.6 29.2±16.7 4.7±3.1 50 44.4 18 0.550 b 0.063 b 0.556 b 0.015 c 0.180 c 0.001 c Data are expressed as Mean±SD (standard deviation). ED: erectile dysfunction, VRF: vascular risk factor, CAD: coronary artery disease, DM: diabetes mellitus, PSV: peak systolic velocity, EDV: end-diastolic velocity, AI: arterial insufficiency, VOD: venoocclusive dysfunction, a : statistically significant, p<0.05, b : one-way ANOVA, c : chi-square test Table 2. Summary of results according to number of vascular risk factors No. of patients PSV EDV AI (%) VOD (%) 1 VRFs 2 VRFs 47 35.8±17.0 4.7±2.9 27.7 27.7 49 34.8±22.4 5.0±2.6 38.8 28.6 3 or more VRFs 42 32.6±20.6 5.7±3.5 47.6 21.4 p-value 0.753 a 0.275 a 0.149 b 0.708 b Data are expressed as Mean±SD (standard deviation). VRF: vascular risk factor, PSV: peak systolic velocity, EDV: enddiastolic velocity, AI: arterial insufficiency, VOD: venoocclusive dysfunction, a : one-way ANOVA, b : chi-square test 포함하여위험인자수에따른혈역동학적지표를비교하였는데단일위험인자군의최고수축기혈류속도와이완기말혈류속도는각각 35.8±17.0, 4.7±2.9 cm/s였고, 두가지위험인자군에서각각 34.8±22.4, 5.0±2.6 cm/s, 그리고세가지이상위험인자군에서각각 32.6±20.6, 5.7±3.5 cm/s로세가지이상위험인자군에서단일위험인자군이나두가지위험인자군에비해최고수축기혈류속도의감소와이완기말혈류속도의증가양상을보였으나통계적으로유의하지는않았다 (Table 2). 고 이연구는심혈관계위험인자가음경혈류지표에미치는영향에대해알아본것으로발기부전환자에서단일위험인자로는관상동맥질환이나당뇨병의기왕력이있는경우음경혈류지표가가장불량하였다. 또한동맥성발기부전은관상동맥질환과당뇨병에서고혈압이나고지혈증보다유의하게빈도가높았는데이는 Kendirci 등 14 의연구에서나온결과와같았으며정맥폐쇄성발기부전의비중이 찰 고혈압환자에서높았던것역시일치했다. 심혈관질환이발기부전의중요한원인으로알려져있으나어떤위험인자가최고수축기혈류속도나이완기말혈류속도등음경혈류지표의이상을보이는지에대한연구는많지않았으며위험인자수에따른변화또한국내에서는연구된적이없었다. 심혈관계위험인자가없는군에서비혈관성발기부전의빈도가가장높았지만심혈관계위험인자가있는환자군에서동맥성발기부전과정맥폐쇄성발기부전의빈도가모두높았으며비혈관성발기부전은적었다. 또한위험인자수가증가할수록수축기혈류속도는감소하고이완기혈류속도는증가하는불량한혈류지표소견을보였다. 발기부전은심혈관질환이발현되기이전에관찰되는전조증상으로생각되고있으며발기부전군에서대조군에비해혈관내피와좌심실의기능이저하된것으로보고된바있다. 19 관상동맥질환은내피세포기능부전과폐색성혈관변화등이원인이되어발생하며특히음경해면체의혈관계에도큰영향을미친다. 혈관내경의감소로인한혈류속도의감소와혈관유순도의감소로인해음경최고수축기혈류의감소를가져올수있으며음경해면체혈류또한감소함으로인해해면체압력이낮아져정맥폐쇄성발기부전도일으킬수있다. 20 당뇨병또한발기부전과깊은연관이있는데일반적으로당뇨병환자의 20-85% 에서발기부전이보고되고있으며, 21,22 Klein 등 23 은당뇨병의기간이길수록, 혈당조절이잘안될수록발기부전이증가한다고보고하였다. 당뇨병환자의경우동맥경화증으로인한혈관변화와신경손상으로발기부전이발생하는데, Benvenuti 등 24 은당뇨병환자에서신경손상보다는혈관폐색이발기부전의원인이라고하였다. 당뇨병환자의음경도플러초음파검사에서정맥폐쇄성발기부전보다동맥성발기부전의유병률이높았는데, 단일위험인자의혈역동학적지표비교를위해환자를
692 Korean Journal of Urology vol. 50, 689-693, July 2009 분류하면서표본수가적어진한계가있어, 당뇨병환자에서혈관성발기부전의정확한양상을알기위해서는더많은데이터가필요할것으로생각한다. 고혈압은혈압상승자체에의한원인뿐아니라동맥경화증과같은혈관직경의변화에의해발기부전이발생하며, Seftel 등 25 의보고에의하면발기부전환자의 40% 에서고혈압이관찰되었으며 Shabsigh 등 26 은발기부전환자 132명을대상으로음경도플러초음파를시행하였는데, 흡연, 당뇨병과함께고혈압의과거력이있는사람에서음경혈류에이상소견을보였다고보고하였다. 본연구에서는고혈압환자가다른심혈관위험인자군에비해상대적으로양호한혈류지표소견을보이면서비혈관성발기부전의비중도높았는데이는상대적으로다른군에비해환자수가많고항고혈압제의사용여부및종류에대한분류가부족한한계점이있었을것으로생각한다. 심혈관계위험인자들의수가증가할수록최고수축기혈류속도의감소와이완기말혈류속도의증가양상을보였으나통계적으로유의하지는않았다. 그러나추가적으로더많은환자를대상로조사한다면유의한결과를보일수도있을것이다. 각위험인자간의부가적인효과나상승효과에대해논의가필요할것으로생각한다. 결 발기부전을호소하는환자들에게음경도플러검사를실시한결과혈관성발기부전으로진단된경우가유의하게많았다. 비혈관성발기부전은심혈관인자가없었던환자군에서유병률이높아유의한차이를보였으며, 동맥성발기부전은관상동맥질환과당뇨병에서유의하게빈도가높았다. 심혈관계위험인자수에따른혈류역동학적변화는더많은환자를대상으로추가적인연구가필요하리라생각한다. 론 REFERENCES 1. NIH Consensus Conference. Impotence. NIH consensus development panel on impotence. JAMA 1993;270:83-90 2. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994;151:54-61 3. Ahn TY, Park JK, Lee SW, Hong JH, Park NC, Kim JJ, et al. Prevalence and risk factors for erectile dysfunction in Korean men: results of an epidemiological study. J Sex Med 2007;4:1269-76 4. Quam JP, King BF, James EM, Lewis RW, Brakke DM, Ilstrup DM, et al. Duplex and color Doppler sonographic evaluation of vasculogenic impotence. AJR Am J Roentgenol 1989;153:1141-7 5. Sattar AA, Wery D, Golzarian J, Raviv G, Schulman CC, Wespes E. Correlation of nocturnal penile tumescence monitoring duplex ultrasonography and infusion cavernosometry for the diagnosis of erectile dysfunction. J Urol 1996;155:1274-6 6. Feldman HA, Johannes CB, Derby CA, Kleinman KP, Mohr BA, Araujo AB, et al. Erectile dysfunction and coronary risk factors: prospective results from the Massachusetts male aging study. Prev Med 2000;30:328-38 7. Bortolotti A, Parazzini F, Colli E, Landoni M. The epidemiology of erectile dysfunction and its risk factors. Int J Androl 1997;20:323-34 8. Roumeguere T, Wespes E, Carpentier Y, Hoffmann P, Schulman CC. Erectile dysfunction is associated with a high prevalence of hyperlipidemia and coronary heart disease risk. Eur Urol 2003;44:355-9 9. Kloner RA. Erectile dysfunction in the cardiac patient. Curr Urol Rep 2003;4:466-71 10. Kim HW, Park WJ, Cho SY. Erectile dysfunction in the patients with cardiovascular disease. Korean J Urol 2006;47: 279-86 11. Yang DH, Jeong JY, Jang SN, Lee SK, Choi YJ, Kim DH. Prevalence and risk factors for erectile dysfunction in aging men: Hallym Aging Study (HAS). Korean J Urol 2007;48: 1258-76 12. Meuleman EJ, Bemelmans BL, van Asten WN, Doesburg WH, Skotnicki SH, Debruyne FM. Assessment of penile blood flow by duplex ultrasonography in 44 men with normal erectile potency in different phases of erection. J Urol 1992;147:51-6 13. Junuzovic D, Mehmedbasic S, Smajlovic F. Color-Doppler ultrasonography in the diagnostic evaluation of erectile dysfunction. Med Arh 2003;57:279-83 14. Kendirci M, Trost L, Sikka SC, Hellstrom WJ. The effect of vascular risk factors on penile vascular status in men with erectile dysfunction. J Urol 2007;178:2516-20 15. McVary KT. Sexual dysfunction in men with lower urinary tract symptoms and benign prostatic hyperplasia: an emerging link. BJU Int 2003;91:770-1 16. Zlotta AR, Schulman CC. BPH and sexuality. Eur Urol 1999;36(Suppl 1):107-12 17. WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004;363:157-63 18. Lewis RW, King BF. Dynamic color doppler sonography in the evaluation of penile erectile disorders. Int J Impot Res 1994;6:A30 19. Uslu N, Eren M, Gorgulu S, Alper AT, Orhan AL, Yildirim A, et al. Left ventricular diastolic function and endothelial function in patients with erectile dysfunction. Am J Cardiol 2006;97:1785-8
Woong Jin Bae, et al:correlation between Cardiovascular Risk Factor and ED 693 20. Kim HW, Park WJ, Choi YS, Cho SY. The correlation between erectile dysfunction and the severity of coronary artery involvement in patients with coronary artery disease. Korean J Urol 2007;48:94-102 21. Son H, Byun SS, Park E, Cho KS, Jo MK, Kim SW, et al. Prevalence of sexual dysfunction in men older than 40 living in Seoul: epidemiologic survey using questionnaire. Korean J Urol 2002;43:52-61 22. Bancroft J, Gutierrez P. Erectile dysfunction in men with and without diabetes mellitus: a comparative study. Diabet Med 1996;13:84-9 23. Klein R, Klein BE, Lee KE, Moss SE, Cruickshanks KJ. Prevalence of self-reported erectile dysfunction in people with long-term IDDM. Diabetes Care 1996;19:135-41 24. Benvenuti F, Boncinelli L, Vignoli GC. Male sexual impotence in diabetes mellitus: vasculogenic versus neurogenic factors. Neurourol Urodyn 1993;12:145-51 25. Seftel AD, Sun P, Swindle R. The prevalence of hypertension, hyperlipidemia, diabetes mellitus and depression in men with erectile dysfunction. J Urol 2004;171:2341-5 26. Shabsigh R, Fishman IJ, Schum C, Dunn JK. Cigarette smoking and other vascular risk factors in vasculogenic impotence. Urology 1991;38:227-31